The endogenous opioid and immune systems are now believed to be intricately linked. The potential, therefore, for opioid drugs to affect, in utero, the developing immune system is of serious concern. This concern is underscored by the association of in utero opioid exposure and perinatal transmission of AIDS. To date, no studies have investigated the immunologic consequences of in utero opioid exposure. We are, therefore, proposing a controlled nonhuman primate study which will elucidate the effects of exogenous opioids on both placental immunoregulation and post natal immunologic function. We will maintain adult female rhesus monkeys on chronic oral regimens of methadone throughout two consecutive pregnancies. Placentas will be collected at term and processed for tissue culture and immunohistochemical studies. Phlebotomy will be performed on the offspring at several postnatal ages and parameters of humoral and cell-mediated immunity evaluated. In addition, in vitro investigation of the role of opioids as cofactors in retroviral transmission will be performed on both placental macrophages and infant peripheral blood lymphocytes. The data from drug exposed placentas and infants will be compared to normative data drawn from age matched animals in our colony. The New England Regional Primate Research Center (NERPRC) is uniquely suited for perinatal investigations in nonhuman primate species. Additionally, the rhesus monkey is an ideal model of human immunoregulation and, because of the cross-reactivity of reagents developed for use in human subjects, can be studied in detail. Moreover, the SIVmac model of AIDS, which is extensively studied at the NERPRC, offers the best nonhuman system for the study of AIDS. Our studies will provide an essential baseline understanding of the immediate and persistent long-term consequences of in utero opioid exposure on the developing immune system and elucidate the potential role of passive addiction in perinatal AIDS transmission. Through such basic research we can eventually develop clinical strategies which will improve the prognosis for passively addicted infants.